The present invention relates to devices used to infuse liquid medication into a patient. More specifically, this invention relates to miniaturization of such devices.
Insulin dependent diabetes mellitus (IDDM) is caused by the autoimmune destruction of the insulin producing islets of Langerhans in the pancreas. Insulin replacement therapy is the interim treatment for IDDM until such time as islet transplants, stem cell treatments, or other improved treatments become feasible. Insulin lowers the concentration of glucose in the blood, while foodxe2x80x94in particular, carbohydratesxe2x80x94raises the concentration of glucose in the blood. The challenge of insulin therapy is to administer food and insulin in a manner that maintains blood glucose concentrations in an acceptable range, avoiding hypoglycemia and hyperglycemia.
Hyperglycemia (high blood glucose concentration) has adverse long-term consequences for the body. These consequences include kidney damage leading to kidney failure, microaneurisms in the retina causing blindness, and the blocking of capillaries in the extremities causing an inability to heal wounds and subsequent gangrene. Hypoglycemia (low blood glucose concentration) has an immediate adverse consequence of reduced brain function that leads to confusion and an inability to reason, remember, or react. In the extreme, hypoglycemia causes seizure, coma, and death.
The first insulin used by diabetes patients was regular insulin taken from beef or pig pancreases. This insulin lasts for about six hours, so that patients were required to inject it three or four times per day. After World War II, longer acting insulin was developed by binding regular insulin to protamine and zinc. Regular insulin dissociates slowly from protamine and zinc, extending insulin action to twelve hours for intermediate acting insulin and twenty-four hours for very long acting insulin. Patients enjoyed reducing injections to one per day, but were required to modify their eating to a snack-all-day regimen to avoid hypoglycemia. The one daily insulin dose was adjusted as needed to reduce the incidence of both hypoglycemia and hyperglycemia.
The development of portable blood glucose meters encouraged the development of more sophisticated insulin therapy regimens. One of these regimens is the split/mixed regiment that consists of two daily doses of mixed regular and intermediate acting insulins taken before breakfast and dinner. These four insulin therapy components are adjusted using blood glucose values measured before each meal and at bedtime. Patients using the split/mixed regimen are required to eat substantially the same meals every day so that the four insulin components may be adapted to the consistent meal pattern over time. Patients on the split/mixed regimen are not only faced with a consistent pattern of what they eat in terms of amount of food, but are also required to eat their meals at particular times. Delay of a meal will result in the patient suffering hypoglycemia
A more recent development in insulin regimen is the basal/bolus regimen, which provides far more flexibility in quantity and timing of meals. The basal/bolus program attempts to emulate the method by which an intact pancreas controls blood glucose. Normally, the intact pancreas produces a steady supply of basal insulin to accommodate the body""s basic insulin needs for glucose secreted at a relatively constant rate from the liver. The pancreas handles meals by releasing a sharp impulse of bolus insulin to accommodate a rapidly rising blood glucose resulting from transformation of carbohydrates (and, to a lesser extent, other food items, especially protein) into blood glucose.
In the basal/bolus regimen, the basal insulin releases are emulated by a once a day injection of a long acting insulin, such as Lantus(copyright), a product of Aventis Pharmaceuticals, or Ultralente(copyright), a product of Eli Lilly and Company. Ultralente is sometimes injected twice daily. These long acting insulins provide the body with a relatively constant supply of insulin. The bolus insulin releases are emulated by bolus injections of fast acting Humalog(copyright) (lispro), or other fast acting insulin. The amount of fast acting insulin taken in an injection must be proportional to the amount of carbohydrate taken with the meal. Some diabetics are able to further fine-tune the injection by calculating the amount of protein, which has a smaller effect on the rise of blood glucose concentration.
To illustrate the basal/bolus regimen in an example, assume a typical diabetic who requires 0.5 units per hour of basal insulin. This person will need a 12-unit injection of long acting insulin daily to cover his or her basal requirements. Timing of such an injection is not critical, and in fact, the long acting insulin is often mixed with the fast acting insulin in one of the bolus injections. Further assume that this typical diabetic""s blood glucose is raised 4 mg/dl (blood glucose concentrations are measured in milligrams per deciliter) for every gram of carbohydrate eaten. This is known as carbohydrate sensitivity. Assume also that a unit of insulin (insulin is measured in xe2x80x9cunitsxe2x80x9d) reduces this typical diabetic""s blood glucose concentration by 40 mg/dl. This is known as insulin sensitivity. The diabetic sits down at a meal and adds up the total grams of carbohydrates in the meal. Assume the meal consists of 80 g of carbohydrates. The diabetic would compute the increase in blood glucose concentration to be (4 mg/dl/g)*(80 g)=320 mg/dl. The diabetic would then compute the amount of bolus insulin required to accommodate, or xe2x80x9ccoverxe2x80x9d this increase, knowing his or her insulin sensitivity. (320 mg/dl)/(40 mg/dl/unit)=8 units. The diabetic would therefore inject 8 units of fast acting insulin before eating the meal.
In practice, exercise, stress, and even unknown factors cause the above calculations to be only approximations. The diabetic, in his or her basal/bolus regimen, usually also needs to adjust the bolus dose taken based upon a blood glucose reading taken prior to the meal. A typical desired target for a diabetic""s blood glucose concentration prior to a meal is 100 mg/dl. xe2x80x9cNormalxe2x80x9d blood glucose concentration range is 80 mg/dl to 120 mg/dl. A blood glucose concentration of 70 mg/dl or lower is usually considered to be hypoglycemic. A blood glucose concentration of 40 mg/dl is dangerously hypoglycemic and the diabetic is usually seriously impaired when his or her blood glucose concentration is at that level. A sustained blood glucose concentration of 20 mg/dl or lower is considered to expose the diabetic to permanent brain damage.
Suppose that, in the example above, the diabetic""s pre-meal blood glucose concentration were 180 mg/dl. The diabetic would recognize that as being 80 mg/dl above the desired concentration of 100 mg/dl. Using the insulin sensitivity in the example, the diabetic would compute the additional insulin required as (80 mg/dl)/(40 mg/dl/unit)=2 units. In the example, the diabetic would then take a 10-unit bolus; 8 for the carbohydrates in the meal, and 2 more to xe2x80x9ccoverxe2x80x9d the fact that the premeal blood glucose concentration was 80 mg/dl above target. If, in the example, the premeal blood glucose concentration were 80 mg/dl (versus a 100 mg/dl xe2x80x9ctargetxe2x80x9d), the diabetic would compute a 0.5 unit negative adjustment (80 mg/dl-100 mg/dl)/(40 mg/dl/unit), and thus take a bolus of 7.5 units with the meal instead of 8 units.
Insulin pumps are mechanisms that allow the basal/bolus regimen to be practiced even more effectively. An insulin pump contains a reservoir of fast acting insulin. Insulin is pumped through a tube from the reservoir into the diabetic. A computer within the pump, with which the diabetic interacts, controls the insulin pump. The diabetic programs in a xe2x80x9cbasal profilexe2x80x9d which tells the pump how much of the fast acting insulin per unit time period to infuse into the diabetic. The pump then infuses this amount into the diabetic in a series of small infusions. In the example above, an infusion rate of 0.5 units per hour was assumed. In practice, this number varies considerably from one individual to the next In some individuals, the rate also needs to vary during the course of a day. In particular, many diabetics find they need a higher rate of infusion for several hours before breakfast. The series of small infusions of fast acting insulin replaces the single injection of long acting insulin as described above. Some insulin pumps infuse a constant microdose at varying time intervals. For example, if the infusion rate is 0.5 units/hour, some insulin pumps will infuse a 0.1 unit microdose five times in a one-hour period. Other pumps will infuse a microdose of varying size, but at constant time intervals. For example, such pumps might infuse a microdose every 3 minutes. The size of each microdose, following the 0.5 unit/hour example, would be (0.5 units/hour)/(20 microdoses/hour), or 0.025 units/microdose.
At a meal, the diabetic makes the same calculations described above for bolus determination, and interacts with the pump to cause it to infuse the proper bolus of fast acting insulin to cover the carbohydrates of the meal, plus or minus any correction that may be needed.
An early insulin pump prototype was introduced in 1963, and was the size of a large backpack. Of course, such a device was impractical because of its size and weight. However, it did demonstrate feasibility of insulin pumps from the standpoint of keeping patients"" blood glucose concentrations in a desirable range.
In the 1970""s miniaturization had progressed to where an insulin pump that was roughly the size of a brick, and weighing about a pound was marketed. The size and weight of such a device was still a very major inhibitor to widespread use. Diabetics simply refused to wear such a heavy and cumbersome device.
In 1980, further miniaturization had reduced the size of a commercial insulin pump to 3.4xe2x80x3xc3x976.3xe2x80x3xc3x971xe2x80x3, weighing 9.6 ounces. Although about ⅓ the size of its predecessors, this pump, too, was too large and awkward for most diabetics.
In the early 1990""s, MiniMed Corporation (now owned by Medtronics Corporation) introduced an insulin pump roughly the size of a pager. The pump was 2xe2x80x3xc3x973.4xe2x80x3xc3x970.8xe2x80x3 and weighted only 3.6 ounces. This pump, and successors having additional features, but of approximately the same physical size, became very popular. Being of xe2x80x9cpager sizexe2x80x9d, these pumps could be worn on belts without being excessively awkward or conspicuous.
Hiding an insulin pump, however, has proved desirable to many people. In response to this desire, a market has arisen for products that hold an insulin pump under clothing. A product made of elastic material and having a pump-sized pouch can be purchased to hold a pump on a user""s calf or thigh. Another product hides a pump in a woman""s bra.
Pump manufacturers have recognized that xe2x80x9csmall is betterxe2x80x9d. However, roughly half the volume of modem pumps is reserved for a reservoir that holds the insulin. Typically, such reservoirs hold 3cc of insulin, which contains 300 units at the insulin concentration most widespread today (U-100). Although more concentrated insulin is known today, and in fact is used in experimental insulin pumps surgically implanted in a diabetic""s body, concern exists with such insulins regarding insulin crystallization in the relatively long tubing through which the insulin must flow between the pump and the body. Such more concentrated insulins are not currently being used in external insulin pumps.
Responsive to demand for smaller insulin pumps, some recent designs have reduced the volume of the insulin reservoir. The MiniMed Paradigm(copyright) insulin pump reservoir, for example, only holds 176 units of insulin, instead of the 300 unit reservoirs that are commonly used in larger pumps. The MiniMed Paradigm(copyright) has succeeded in attaining a 37% reduction in pump size, largely due to the use of the smaller reservoir.
Use of a smaller reservoir, however, can result in required more frequent changes of the reservoir and tubing. Most diabetics change their reservoir, tubing, and infusion set (collectively called xe2x80x9cdisposablesxe2x80x9d) approximately every three days. An infusion set comprises a canula inserted into the body. The infusion set also comprises tape or other means to attach the infusion set to the body. Less frequent changes raises risk for infection and scarring of tissue where the infusion set is inserted into the body. More frequent change increases the annual cost of treatment.
The conventional process of changing a reservoir, tubing, and infusion set comprises the steps of filling the reservoir from a vial, attaching the tubing to the reservoir, and filling the tubing from the reservoir. A 42xe2x80x3 length of tubing holds approximately 26 units of insulin. In addition, the infusion set requires approximately 1 to 3 units of insulin. The previously used tubing and infusion set and the insulin they contain, are discarded when changing the disposables. After filling a 42xe2x80x3 tubing and the infusion set from the reservoir, the reservoir contains 26 fewer units of insulin than were drawn from the vial, further, less the 1 to 3 units that were discarded in the infusion set. In the case of the MiniMed Paradigm(copyright), although 176 units were drawn from the vial to fill the 176-unit reservoir, less than 150 units can be infused into the diabetic. The remaining units are discarded, along with the tubing and infusion set, when the disposables are replaced. Almost ⅓ of type-1 diabetics require more than 50 units/day of U-100 insulin. Furthermore, insulin pumps are beginning to be marketed to type-2 diabetics. Type-2 diabetics are often xe2x80x9cinsulin resistantxe2x80x9d, that is, needing more insulin per gram of carbohydrate, and therefore require more insulin per day than type-1 diabetics. Any diabetic requiring even slightly more than 50 units/day, in the case of the Paradigm(copyright) pump, will need to change their disposables more often than every three days, incurring unnecessary expense, as well as the inconvenience of changing the disposables more frequently.
Although insulin infusion pumps were used for exemplary purposes above, any medical infusion device, especially medical infusion devices that must be worn by patients, are desirably as small as possible, and therefore, share the same problem of making the best use of the volume of the reservoir that holds the medication.
Therefore, a need exists to make more efficient use of the capacity of a reservoir in a medical infusion device.
The present invention discloses an apparatus and method that allows a quantity (volume) of medication substantially equal to the entire volume of a reservoir to be infused into the patient.
In a first embodiment, a method is disclosed to allow infusion of a quantity of medication that is substantially equal to the entire quantity of medication held in a reservoir, wherein medication from a vial of medication is drawn through a quick-release syringe into a tubing coupled to a reservoir, to fill the volume of the tubing, and, optionally, some of the volume of the reservoir. Subsequently, the tubing is detached from the reservoir, a reservoir syringe is attached to the reservoir, and the reservoir is xe2x80x9ctopped offxe2x80x9d with medication from the vial. Then the reservoir syringe is detached from the reservoir. Finally, the tubing is reattached to the reservoir, an infusion set is coupled to a distal end of the tubing, and the infusion set is primed (filled) with medication. At that point, a cannula on the infusion set is inserted into the patient""s body, and the infusion set is affixed by adhesive or other means to the patient""s body. Because both the reservoir and the tubing are full, a volume of medication equal to substantially all of the volume of the reservoir can be infused into the patient.
In another embodiment, a method that will allow infusion of a quantity (volume) of medication that is substantially equal to the entire volume of a reservoir, is disclosed wherein medication from a vial of medication is drawn through a reservoir syringe attached to a reservoir. Subsequently, the reservoir syringe is detached, and a tubing is attached to the reservoir. The tubing is filled from the reservoir. Then, the tubing is detached from the reservoir, the reservoir syringe is reattached to the reservoir, and the reservoir is xe2x80x9ctopped offxe2x80x9d from the vial of medication. The reservoir syringe is again detached. The tubing is reattached to the reservoir. An infusion set is coupled to a distal end of the tubing, and the infusion set is primed with medication. At that point, a cannula on the infusion set is inserted into the patient""s body, and the infusion set is affixed by adhesive or other means to the patient""s body. Because both the reservoir and the main tubing are full, a volume of medication equal to substantially all of the volume of the reservoir can be infused into the patient.
The Funderburk patent cited earlier discloses a xe2x80x9cquick-connect coupling for a medication infusion systemxe2x80x9d. A quick-release syringe improvement of the coupling disclosed in Funderburk is disclosed herein as an apparatus used in the present invention. The novel quick-release syringe disclosed couples with a quick-release portion on a distal end of the tubing. Medication is drawn from a vial of medication through the quick-release syringe, filling the tubing and, optionally, a portion of a reservoir.
In another apparatus embodiment, a tubing has a first quick-release coupling portion at a proximal end of the tubing and a second quick-release coupling portion at a distal end of the tubing. A short air elimination tubing is disclosed that has a first end suitable for attaching to a reservoir and a second end having a third quick-release coupling portion suitable for coupling to the first quick-release coupling portion. The short air elimination tubing allows removal of any air that might enter when the first end of the air elimination tubing is attached to the reservoir. Advantageously, the air elimination tubing is short and contains only a small amount of medication, preferably less than approximately 1% of the volume of a reservoir in a medication infusion device. Although the volume of the air elimination tubing is preferably approximately 1% or less of the volume of the reservoir, longer air eliminating tubings can be used, although with reduced advantage of the invention.
Even if the air elimination tubing volume is approximately 3% or 6% of the volume of the reservoir, a larger quantity of medication can be infused into the patient from a given reservoir than when using prior methods.